P367: LONG-TERM OUTCOMES OF ADULTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH BREXUCABTAGENE AUTOLEUCEL IN ZUMA-3 BY AGE, PRIOR THERAPIES, AND SUBSEQUENT TRANSPLANT
Authors: Bijal Shah, Ryan D. Cassaday, Jae H. Park, Roche Houot, Olalekan O. Oluwole, Aaron C. Logan, Nicolas Boissel, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Kristen M. O’dwyer, Maria R. Baer, Gary J. Schiller, Mehrdad Abedi, Monique C. Minnema, Patrick Stiff, Lang Zhou, Tsveta Hadjivassileva, Rita Damico Khalid, Armin Ghobadi
Journal: HemaSphere (2023)

Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the US for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and in the EU for adults ≥26 years of age with R/R B-ALL based on positive results of ZUMA-3. After 3 years of follow-up in ZUMA-3, brexu-cel demonstrated an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 71% and a median overall survival (OS) of 26.0 months in all treated patients (N=55) and 38.9 months in patients with CR (n=31; Shah et al. EU CAR T 2023. Abstract 34). Aims: Here, we report 3-year outcomes by age, number of prior therapies, prior blinatumomab, and subsequent allogeneic stem cell transplant (alloSCT). Methods: Patients (≥18 y) had R/R B-ALL and received a single brexu-cel infusion (1×10⁶ CAR T cells/kg) following leukapheresis and conditioning chemotherapy. The primary endpoint was overall CR/CRi rate per independent review. Post hoc subgroup analyses were exploratory, with descriptive statistics reported. Results: As of July 23, 2022, the median follow-up in Phase 2 (N=55) was 38.8 months (range, 32.7-44.6). The CR/CRi rate (95% CI) was 67% (35-90) for patients <26 years (n=12) and 72% (56-85) for patients ≥26 years (n=43). The median (95% CI) OS was 28.6 months (0.6-not estimable [NE]) for patients <26 years and 34.1 months (15.9-NE) for patients ≥26 years. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 92% of patients <26 years and in 88% of patients ≥26 years. For patients with 1 prior therapy (n=10), the CR/CRi rate was 90% (95% CI, 55-100) and for patients with ≥2 prior therapies (n=45), the CR/CRi rate was 67% (95% CI, 51-80); medians (95% CI) for OS were not reached (NR; 2.1-NE) and 25.6 months (14.2-38.9), respectively. The incidence of Grade ≥3 TRAEs was 90% for patients with 1 prior therapy and 89% for patients with ≥2 prior therapies. The CR/CRi rates (95% CI) for patients with (n=25) and without (n=30) prior blinatumomab were 60% (39-79) and 80% (61-92). The median (95% CI) OS was 14.2 months (3.2-26.0) for patients with prior blinatumomab and NR (18.6-NE) for patients without prior blinatumomab; Grade ≥3 TRAEs occurred in 80% and 97% of patients, respectively. For responders (CR/CRi) who did (n=10) or did not (n=29) proceed to subsequent alloSCT, the median (95% CI) OS was NR (7.6-NE) and 38.9 months (18.6-NE), respectively. Similar efficacy results were observed in a pooled subgroup analysis of Phase 1 and 2 patients treated at the pivotal dose (N=78), with a median follow-up of 41.6 months (range, 32.7-70.3). Summary/Conclusion: Adults with R/R B-ALL benefitted from brexu-cel, regardless of age, number of prior therapies, prior blinatumomab exposure, or subsequent alloSCT status. Survival appeared longer in patients with fewer prior therapies and in blinatumomab-naïve patients; however, small patient numbers and unmatched baseline characteristics limit interpretation of these results. Additional studies are needed to determine the impact of prior therapies and/or subsequent alloSCT on outcomes of patients who receive brexu-cel. Keywords: Hematopoietic cell transplantation, Relapsed acute lymphoblastic leukemia, CAR-T, CD19